Project Summary The Berkeley Center for Structural Biology (BCSB) operates five highly-productive macromolecular crystallography beamlines at the Advanced Light Source. One of these beamlines, 5.0.1, received a Pilatus3 6M detector as part of a High-End Instrumentation grant in 2016, and the impact on beamline performance and capabilities has been enormous. However, the Pilatus 6M is only temporarily at 5.0.1, since it was acquired for the new microfocus beamline, Gemini. It will be moved to Gemini in early 2019 as per the original plan presented to NIH for the instrumentation grant. We are thus seeking funding for a Pilatus3 2M detector for beamline 5.0.1 in order to maintain the enormous increase in productivity and the new automation features that a fast-framing pixel array detector enables for our large user community. The gain in speed, quantum efficiency, sensitivity, and dynamic range of these systems over most current CCD detectors is significant, and in fact critical to the success of many structural biology projects. The fast readout time enables fine phi slicing mode of data collection while minimizing radiation damage, and allows extremely high throughput so that many more samples can be analyzed. The large dynamic ranges means that both strong and weak reflections can be collected simultaneously, which also minimizes radiation damage and increases throughput. The fact that a reflection can be captured on a single pixel, due to the very small point spread function, effectively reduces spot size on the detector. We have calculated that with a Pilatus3 2M on 5.0.1, the closest approach of the detector to the sample is 120 mm, enabling the capture of 1.15 resolution diffraction spots. This makes the requested Pilatus3 2M detector an extremely important and cost-effective instrumentation advance for the beamline.